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2/10
What did I miss?

3 decades of fateful trials of ERAs in PAH, HTN, DKD, FSGS & IgAN (AFFINITY, ALIGN) set the stage for

PROTECT
SparsentanIrbesartan
https://thelancet.com/journals/lancet/article/PIIS0140-6736(23)00569-X/fulltext (PMID 37015244)

Phase 3 RCT
Active-controlled
Double-blind

18 countries
134 sites

The cohort

3/10
1 toot methods

n=406
270 weeks (114+156 weeks open label with SGLT2i!)

Carefully selected population for nil significant cardio/cerebro-vascular or hepatic disease
On MLD/50% MLD of RAASi
1:1 randomisation
Stratification as per eGFR & proteinuria
MMRM statistics

4/10
1 toot results

After 36 weeks of Sparsentan
41% relative reduction in UPCR
Lesser number reached 40% reduction of eGFR, kidney failure or all-cause mortality

Freq adverse effects in both groups! (88% vs 78%)

Similar body weight changes/use of diuretics/BP

5/10
A figure paints 1000 words

Geometric least square mean ratio between groups was 0.59 (CI 0.51-0.69)

Maximal slope of reduction of proteinuria achieved at week 4, continued to accrue up to week 36

Additionally, proteinuria reduction was similar across all sub-groups!

7/10
#NephJC Chat consensus?

We need more data & accelerated approvals using surrogate end-points may not be a bad thing at all.

& Ahem, after rigorous trials & rounds of approval, there's the formidable next challenge- COST!

Very adequately put by @hswapnil (https://twitter.com/hswapnil/status/1661188894526717952?s=20)

8/10
Quote (Question) of the fortnight (decade really):

Will we ever have an answer? Unless we look systematically at the natural course/course on non-immunosuppressive or immunosuppressive therapy by doing serial biopsies? #NephJC
From Richard Glassock https://twitter.com/GlassockJ/status/1661315990389657600?s=20

9/10
I want more info:

#NephJC summary by Anitha Swamy & Saumya Vishnoi
http://www.nephjc.com/news/sparsentan-protect

Visual Abstract below by
Saumya Vishnoi
http://www.nephjc.com/news/2023/5/23/protect-study-on-sparsentan-in-igan-visual-abstract

Tweetorials covering the topic
https://twitter.com/ckd_ce/status/1521464649069301760?
https://twitter.com/ckd_ce/status/1508757986868559875?s=20 s=20

10/10
#NephJC 10 Toot Final thoughts

Sparsentan (FILSPARI) holds promise.
Convincing biological plausibility
Favourable reduction in proteinuria
Early onset effect
Comparable side-effect profile
Safety in study group (though carefully selected)

"Hope is a good thing, maybe the best!"

Next #NephJC Chat is

'Intravenous Sodium Thiosulphate for Calciphylaxis of Chronic Kidney Disease: Systematic Review and Meta-analysis'
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2804210

Join us on June 20th and 21st

#TenTweetNephJC by @SayaliBThakare brought to med-mastodon by @jmteakell :)

The #NSMC never sleeps by Momen Abbasi